Melanins are a class of structurally related chemicals which are the principal pigments of mammalian skin and hair. Melanins are synthesized by specialized cells termed "melanocytes" or "pigment cells", which are found in the skin and hair follicles. Melanocytes respond to ultraviolet radiation, for example, that found in sunlight, by going through cell divisions and by producing more melanin. The net result of exposure to ultraviolet radiation is therefore an increase in the number of melanocytes and an increase in melanin content of the skin. This entire process is known commonly as "sun tanning." The ability of human beings to sun-tan is of great medical significance because it has been well-documented that light-skinned individuals are much more susceptible to sun-induced skin cancers than are dark-skinned individuals. Sun-tanning is also of great social significance in that in many parts of the world increased melanin pigmentation is aesthetically desirable. However, for many individuals sun-tanning is difficult to achieve without concommitant erythema (i.e., sunburn) and resultant peeling of the skin.
Other individuals are unable to achieve an acceptable sun tan due to their being afflicted with vitiligo which is a disorder of unknown origin which results in the acquired loss of melanocytes in various areas of the skin. The net result of vitiligo is, in the extreme, total depigmentation of skin and hair. More commonly, vitiligo results in patchy white areas of the skin and hair. In dark-skinned individuals vitiligo can cause severe cosmetic problems and resultant psychological stress. Vitiligo afflicts about 1% or 40 million, of the world's population. A prime treatment for vitiligo is with psoralens and ultraviolet radiation which results in an increase in the number of melanocytes and melanin production in the patchy white areas of the skin. However, psoralens are toxic--causing dermatitis and necrosis when applied to the skin and hepatic insufficiency and nervous and digestive disorders when ingested. There is also evidence that psoralens pklus ultraviolet light will induce skin cancer.
Thus, it has long been desired to find a means of effecting an increased accumulation of melanin in the skin and hair of humans and other mammals without the concommitant disadvantages described above, e.g., erythema and/or skin cancer or other toxic effects.
In order to avoid the aforementioned disadvantages of exposure to the sun, it has been proposed to use solar filters (i.e. sun screening agents) whereby the amount of erythema causing radiation reaching the skin is diminished. However, in some cases the sun screening agents reduce the total amount of radiation to the point where the rate of tanning is decreased to an undesirably low level. Thus, many persons desiring a rapid tan are discouraged from using sun screens.
In an attempt to achieve a tanning effect without the above-indicated disadvantages of exposure to UV irradiation and without the use of solar filters in U.S. Pat. No. 2,949,403, for example, it has been proposed to use a composition comprising dihydroxyacetone to effect a "simulated" tan on the skin. This composition by effecting the so-called tan through its reaction with the proteinaceous components of the skin obviates the need for exposure to the sun thereby preventing the deleterious effects of such exposure as defined above. However, use of the above composition suffers from numerous disadvantages. It frequently results in different shadings on the skin due to uneven application. Furthermore, the colored areas are non-uniformly removed during cleaning of the skin.
A number of compositions useful for enhancing coloration of the skin due to exposure to the sun have been proposed in e.g., U.S. Pat. No. 4,293,542 wherein pyridinyl oxide derivatives are disclosed which function at UV wavelengths outside the erythemal range thus permitting use of sun-screening agents while facilitating rapid tanning without the usual concommitant effects of exposure to the shorter UV wavelengths.
In U.S. Pat. No. 4,228,151 there are disclosed various quinoxaline derivatives which may be used in a similar manner. However, the above compositions require that melanocytes be present in the epidermis in order that exposure to UV radiation be able to effect the coloration of the epidermis. If, however, such melanocytes are not present in the epidermis tanning or melanization can not occur despite administration of the aforementioned composition and exposure to UV radiation. Thus, persons having low, or no, concentrations of melanocytes in the epidermis (e.g., vitiligo victims) could not achieve melanization of the epidermis by using the compositions disclosed in the prior art.
Furthermore, in U.S. Pat. No. 4,021,538 there are described compositions for "producing pigmentation in . . . skin" comprising the salts of aliphatic esters of DOPA or .alpha.-methyl DOPA. In order to effect the desired pigmentation the above salts must be oxidized, in alkaline media prior to topical application to the subject or by in vivo oxidation by means of topical application of additional oxidizing agents.
The present invention provides compounds useful in preparing compositions which increase the number of melanocytes and the production of melanin in mammalian skin even in the absence of exposure to UV radiation.
It has now been found, in accordance with this invention, that increased natural melanization of the epidermis can be achieved without adverse effects, even in persons having no epidermal melanocytes, by administering to such persons the composition according to the instant invention in the absence of exposure to UV radiation.